The accumulation of alpha-synuclein fibrils within Lewy bodies and Lewy neurites is the defining feature of idiopathic Parkinson's disease (PD). Alpha-synuclein has been implicated in disease pathogenesis with the discovery of dominantly inherited alpha-synuclein gene (SNCA) mutations in rare familial versions of PD.
The development of dementia in PD is associated with more widespread accumulation of aggregated alpha-synuclein protein, particularly accumulation in neocortical regions responsible for higher cognitive function. Over 60% of patients with PD and dementia have widespread accumulation of a second aggregated protein, Abeta, which is a defining feature of Alzheimer's disease (AD). In AD, Abeta accumulation occurs in combination with aggregated tau protein accumulation; however, widespread tau deposition only rarely occurs in PD.
Interestingly, our recent cerebrospinal fluid (CSF) studies in people with PD indicates altered metabolism of both alpha-synuclein and Abeta. Furthermore, a correlation between decreased CSF levels of the two proteins suggests a link between changes in their metabolism.
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